Medical Conditions

STARGARDT DISEASE

Untreatable and Leading Cause of Childhood Blindness

Stargardt disease is a rare yet life devastating condition. It is the most common form of
inherited macular degeneration, and affects about one in 10,000 people
(about 30,000 people in the United States).
There is currently no cure or treatment for Stargardt disease and clinical trials such as our ongoing Phase 2 study, as well as trials
assessing other modalities (gene or cell therapies for example) are currently undergoing.
Patients with Stargardt most often start experiencing significant vision loss during
their childhood and teenage years (60% of the patients are diagnosed before 20 years of age).
This vision loss cannot be corrected by glasses, and diagnosis had been traditionally delayed due to the young age
of the patients and the rareness of the disease.
After diagnosis, and depending on age at onset, vision deteriorates progressively to levels
below 20/200 (legal blindness). The disease
affects mostly the central vision and spares some of the peripheral vision, although there are very severe
forms that lead to complete blindness.
Almost all of those affected by Stargardt disease will live legally blind during their adult lives,
although patients with late onset may retain some visual acuity.
Loss of central vision leads to impossibility to perform tasks such as reading, writing, driving or recognizing faces.

In 1997, scientists discovered that Stargardt disease results from a defective gene, the ABCA4,
responsible for the synthesis of an important protein called Rim protein. A normally functioning Rim protein
transports vitamin A molecules from the photoreceptors (the molecules sensitive to light) back into specialized
cells (called RPE), where vitamin A molecules are recycled to be reused for vision. In Stargardt,
the defects in the ABCA4 gene lead to partial or full dysfunction of this protein.
As a result, vitamin A transport is affected and vitamin A molecules tend to accumulate
in the photoreceptors. This accumulation
leads to the formation of toxic pigments (known as "vitamin A dimers")
believed to be partly responsible
for vision loss. Although normal individual also form vitamin A dimers, this process usually
takes decades, explaining why age-related macular degeneration (AMD) occurs later in life of normal people,
while the same process takes only a few years in Stargardt explaining vision loss from childhood.

If the involvement of vitamin A dimers in Stargardt is now relatively well accepted and if genetic tests
can now accurately diagnose the disease, there has been unfortunately little attention paid to Stargardt
compared to the more prevalent AMD. An explanation could be that Stargardt is a very rare disease
with few patients compared to other diseases, making it less attractive for pharmaceutical companies to develop
a treatment for this disease. Rare diseases are therefore called "orphan diseases" due to this lack of
interest from drug developers.

Alkeus Pharmaceuticals is committed to searching and developing cures or treatments for serious
ophthalmic conditions, and despite
its rareness, a treatment for Stargardt disease would have a major impact on the lives of hundreds of thousands
of people worldwide, particularly as patients with Stargardt lose vision from as early as 6 and would
benefit the most from a treatment that could slow or stop the progression of vision loss.
Such a treatment is generally called a "disease modifying drug", as it
has the potential to alter the course of the disease and slow it down. It is unknown whether a disease modifying
drug could also help restore some of the lost vision.

In addition, due to similarities between Stargardt and dry-AMD,
a better understanding of Stargardt disease could undoubtedly contribute to better understanding
of dry-AMD and perhaps help develop a novel treatment that could save
millions of people with dry-AMD.

Alkeus Pharma's lead compound, ALK-001, is an oral compound with a well-understood mechanism of action.
ALK-001 was specifically designed to prevent the formation of these toxic vitamin A dimers
in the eye. If a benefit was observed in mice studies, long term clinical trials are now necessary to assess
whether ALK-001 has a benefit in the treatment of Stargardt disease. ALK-001
has been cleared by the U.S. Food and Drug Administration (FDA) to start a clinical trial.
Clinical trials are needed to assess the safety and effectiveness of a drug.